Mechanical penetration of β-lactam-resistant Gram-negative bacteria by programmable nanowires.

Liu, Lizhi; Chen, Sheng; Zhang, Xu; Xue, Zhenjie; Cui, Shengjie; Hua, Xiaoting; Yang, Baowei; Yan, Huiling; Liu, Cong; Wang, Jing; Zhang, Zengfeng; Yu, Wei; Wu, Fan; Xu, Wujun; Lehto, Vesa-Pekka; Yue, Tianli; Liu, Yan; Yu, Yunsong; Wang, Tie; Wang, Jianlong

β-Lactam-resistant (BLR) Gram-negative bacteria that are difficult or impossible to treat are causing a global health threat. However, the development of effective nanoantibiotics is limited by the poor understanding of changes in the physical nature of BLR Gram-negative bacteria. Here, we systematically explored the nanomechanical properties of a range of Gram-negative bacteria (Salmonella, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) with different degrees of β-lactam resistance. Our observations indicated that the BLR bacteria had cell stiffness values almost 10× lower than that of β-lactam-susceptible bacteria, caused by reduced peptidoglycan biosynthesis. With the aid of numerical modeling and experimental measurements, we demonstrated that these stiffness findings can be used to develop programmable, stiffness-mediated antimicrobial nanowires that mechanically penetrate the BLR bacterial cell envelope. We anticipate that these stiffness-related findings will aid in the discovery and development of novel treatment strategies for BLR Gram-negative bacterial infections.